International Journal of Organ Transplantation Medicine Outcomes of Patients with Portal Vein Thrombosis Undergoing Live Donor Liver Transplantation

Background: Live donor liver transplantation (LDLT) for patients with portal vein thrombosis (PVT) creates several technical challenges due to severe pre-operative condition and extensive collaterals. Although deceased donor liver transplantation in patients with PVT is now routinely performed at most centers, the impact of PVT on LDLT outcomes is still controversial.


INTRODUCTION
P ortal vein thrombosis (PVT) is a common complication associated with cirrhosis; its prevalence is between 0.6% and 15% [1][2][3][4][5]. PVT used to be an absolute contraindication for liver transplantation. However, advances in surgical techniques and patient care make it possible to overcome PVT during liver transplantation. In the recent years, innovative surgical techniques such as thrombectomy, use of venous jump graft, and use of portal vein tributaries have been proposed to overcome the operative challenges.
Live donor liver transplantation (LDLT) in patients with PVT has its own difficulties such as need for distal dissection of vascular pedicle of the hilum and restricted availability of a vein graft. The presence of PVT in the recipient has frequently been considered as a controversial issue for LDLT candidates. During surgery, the initial attempt to overcome PVT is thrombectomy, which is successful in the majority of cases. However, failed thrombectomy may necessitate vessel grafting. Vascular conduits can easily be obtained from the donor during the process of deceased donor liver transplantation. Therefore, the only kinds of vascular grafts left that can be utilized in LDLT are autologous, cryopre-served vessel graft, and prosthetic graft. Autologous vascular grafts are ideal because they carry no immunogenicity risk.
In this report, we analyze the outcome of adult patients with PVT who underwent LDLT in the USA from 1998 to 2009.

MATERIALS AND METHODS
We retrospectively queried the Scientific Registry of Transplant Recipients (SRTR) database for adult patients with PVT who underwent LDLT in the USA from 1998 to 2009. Patients who had liver retransplantation or pediatric LDLT were excluded from the study.
In the SRTR database, PVT status is reported at two different times; it is reported for liver transplant candidates (recorded as of the time of listing) and for transplant recipients (recorded as of the time of transplant). For analysis involving transplant recipients, the data of the latter field has been used. Occasionally, the PVT field in the candidate and recipient files did not correlate (2.0% of patients). We did not specifically make adjustments when the two PVT covariates were not in agreement. The data on pre-operative assessment of PVT was not available in the database. We collected the following information under recipient in both groups: patient age, sex, MELD score, hospital length of stay, waiting time prior to transplantation, recipient wait, recipient body mass index (BMI), rejection at one year, and retransplantation rate. The information collected on the donor included donor age, weight, BMI, and sex. Missing values were imputed with the mean values.
Statistical analysis χ 2 and Student's t tests were used for comparison of proportions and means, respectively. Graft and patient survival was the primary outcome measured. Kaplan-Meier survival analysis was used for allograft and patient survival estimates. Continuous variables were

RESULTS
There were 2402 adult patients who underwent LDLT from 1998 to 2009. The cohort, was then divided to those with (n=68) and without PVT (n=2334). The incidence of PVT  Overall, patients with PVT had worse allograft and patient survival when compared with those without PVT (Fig 1). In Cox regression analysis, PVT was associated with worse allograft survival (HR=1.7, 95% CI: 1.2-2.5, p<0.001) and patient survival (HR=1.6, 95% CI: 1.2-2.4, p<0.001) compared to non-PVT patients (Table 2). However, there was a marked improvement in the results of LDLT for PVT comparing the first 34 cases with the second 34 cases to address the learning curve issue (Fig 2).

DISCUSSION
Several groups have reported favorable results in patients with PVT who underwent liver transplantation, and have described effective strategies for the management of PVT during liver transplantation [1][2][3][4][5]. PVT is, therefore, no longer a contraindication for liver trans-plantation.
LDLT has emerged as a solution to overcome the current organ shortage. The presence of PVT in the recipient has frequently been presented cautionary measure for LDLT by some groups based on the greater obstacles [6][7][8].
Pre-existing complete PVT creates considerable challenges during the surgery. The majority of centers consider PVT a relative contraindication for LDLT [8]. In this study, 2.8% of patients who underwent LDLT in the USA from 1998 to 2009 had PVT.
Another major concern in liver transplantation in patients with PVT is postoperative portal vein rethrombosis-6.2% to 28.6% of patients developed rethrombosis. Anticoagulation therapy to prevent portal vein rethromobosis after liver transplantation remains controversial, but it could be considered in high risk patients or for recanalization of PVT after liver transplantation. 7 Taken together, depending on PVT grading and the experience of the surgeon, various surgical techniques can be performed during liver transplantation to restore adequate portal flow to liver allograft in patients with PVT,. Thrombectomy with direct portal vein anastomosis is the most commonly used operative approach [6][7][8]. Jump venous graft from the superior mesenteric vein is only indicated for the restoration of portal flow in cases of extensive PVT [8,9]. Moreover, to ensure successful transplantation in patients with PVT, preoperative evaluation and thorough operative planning are essential. If PVT  is extensive, re-establishment of portal flow needs complex vascular reconstruction. Specifically, in LDLT, the surgical techniques reported for the management of PVT include thrombectomy, jump graft to superior mesenteric vein or left renal vein [9], utilization of umbilical portion of recipient's left portal vein [10], use of saphenous vein interposition graft [11], recipient's explanted native right hepatic vein [12], and left gastric vein and iliac vein conduit from a deceased donor [13].
Previous single-center studies showed that the long-term outcome of patients with PVT who underwent LDLT, is comparable with that of patients without PVT [9,15,16]. Our study showed that patients with PVT who underwent LDLT had longer hospital stay and higher retransplantation rate. In addition, overall, allograft and patient survival was inferior comparing patients with and without PVT who underwent LDLT. PVT recipients were older, but had comparable MELD scores compared to non-PVT patients in this study.
Our study showed that PVT is a risk factor for poor allograft and patient outcomes. Patients with PVT who underwent LDLT had early allograft lost and patient mortality (Fig  1), which could be due to post-operative complications or operative challenges. However, long-term survival can still be achieved in these patients. The outcome of patients with PVT who underwent LDLT has improved comparing the first 34 cases with the most recent 34 cases. This possibly can be explained with improvement in surgical technique, experience and peri-and post-operative care.
This study has several limitations. First, it is a retrospective analysis of SRTR data. We recognize both potential advantages and limitations of this study that use a large national database. However, the large sample size provides sufficient power to detect significant independent risk factors that may be missed by single-center studies. As with any analysis utilizing the SRTR database, our conclusions rely on the assumption that there is no systematic bias generated by reporting error or missing data. The groups were extremely unequal in size, selection criteria for one or the other procedures are not known. However, the primary endpoint for this analysis was allograft and patient survival, which is reliably captured in the SRTR database. Residual or unmeasured confounders that could impact allograft and patient survival include: surgeon technique, differences in immunosuppression protocols, the fat content/quality of the allograft and center-specific practices. Other important determinants of success with LDLT, such as recipient and donor selection, graft weight and quality, GWRW ratio, surgical details, techniques employed to treat PVT, degree of PVT (partial vs complete), center and surgeon volume/experience were not available in the database.
In conclusion, the US experience (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009) showed that outcomes of patients with PVT who underwent LDLT were inferior to those without PVT. The lower allograft and patient survival should be taken into consideration in the overall debate regarding the choice of LDLT vs deceased donor liver transplantation in patients with PVT. LDLT should be performed under protocol and studied in experienced centers for patients with PVT.